• Hiroyuki Kinoshita, Naoyuki Matsuda, Hikari Kaba, Noboru Hatakeyama, Toshiharu Azma, Katsutoshi Nakahata, Yasuhiro Kuroda, Kazuaki Tange, Hiroshi Iranami, and Yoshio Hatano.
• Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan. hkinoshi@pd5.so-net.ne.jp
• Hypertension. 2008 Sep 1;52(3):507-13.

AbstractThe present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.

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